FBXO32 links ubiquitination to epigenetic reprograming of melanoma cells - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Cell Death and Differentiation Année : 2020

FBXO32 links ubiquitination to epigenetic reprograming of melanoma cells

Résumé

Ubiquitination by serving as a major degradation signal of proteins, but also by controlling protein functioning and localization, plays critical roles in most key cellular processes. Here, we show that MITF, the master transcription factor in melanocytes, controls ubiquitination in melanoma cells. We identified FBXO32, a component of the SCF E3 ligase complex as a new MITF target gene. FBXO32 favors melanoma cell migration, proliferation, and tumor development in vivo. Transcriptomic analysis shows that FBXO32 knockdown induces a global change in melanoma gene expression profile. These include the inhibition of CDK6 in agreement with an inhibition of cell proliferation and invasion upon FBXO32 silencing. Furthermore, proteomic analysis identifies SMARC4, a component of the chromatin remodeling complexes BAF/PBAF, as a FBXO32 partner. FBXO32 and SMARCA4 co-localize at loci regulated by FBXO32, such as CDK6 suggesting that FBXO32 controls transcription through the regulation of chromatin remodeling complex activity. FBXO32 and SMARCA4 are the components of a molecular cascade, linking MITF to epigenetics, in melanoma cells.

Domaines

Cancer
Fichier principal
Vignette du fichier
s41418-020-00710-x.pdf (2.46 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

inserm-03138835 , version 1 (11-02-2021)

Identifiants

Citer

Nadia Habel, Najla El-Hachem, Frédéric Soysouvanh, Hanene Hadhiri-Bzioueche, Serena Giuliano, et al.. FBXO32 links ubiquitination to epigenetic reprograming of melanoma cells. Cell Death and Differentiation, 2020, Online ahead of print. ⟨10.1038/s41418-020-00710-x⟩. ⟨inserm-03138835⟩
61 Consultations
52 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More